Functionalization of biopolymers with growth factor-binding peptides

Abstract

The disclosure relates to a biopolymer that is functionalized with a peptide, preferably a growth factor-binding peptide. The disclosure further relates to a device comprising a functionalized biopolymer, to methods for treatment of a tissue pathology in a subject using a device according to the disclosure, to methods for coupling peptides to carbonyl groups of a biopolymer, and to a use of oxygen plasma for coupling a peptide to carbonyl groups of a biopolymer.

The invention claimed is: 
     
       1. A biopolymer that is functionalized with a peptide,
 wherein the biopolymer is a synthetic polyester, 
 wherein the peptide comprises KGLPLGNSH (SEQ ID NO:3), wherein the number of amino acid residues in the peptide is up to 50; and 
 wherein the peptide is coupled to a carbonyl group of the non-functionalized biopolymer through binding of an N-terminal amino group of the peptide, or through binding of an amino group in a side chain of the N-terminal lysine of the peptide. 
 
     
     
       2. The biopolymer of  claim 1 , wherein the peptide is present on the biopolymer in a concentration-gradient. 
     
     
       3. The biopolymer of  claim 1 , wherein the biopolymer is selected from the group consisting of polylactic acid, poly-L-lactic acid, polyglycolic acid, polyglycolic lactic acid, poly(caprolactone), polyalkyleneoxide-polyalkylene-terephthalate block copolymer, polyesters, polyethylene terephthalate (PET), polybutylene A terephthalate (PBT), polytrimethylenecaprolactone (PTMC) and/or combinations thereof. 
     
     
       4. The biopolymer of  claim 1 , wherein the polyester is poly(caprolactone). 
     
     
       5. The biopolymer of  claim 1 , wherein the peptide is coupled to the carbonyl group of the non-functionalized biopolymer through binding of an amino group in a side chain of the N-terminal lysine of the peptide. 
     
     
       6. A device comprising the biopolymer of  claim 1 . 
     
     
       7. A method of treating an injured tendon and/or ligament, the method comprising:
 utilizing the biopolymer of  claim 1  in the treatment of an injured tendon and/or ligament. 
 
     
     
       8. A biopolymer, the biopolymer comprising a synthetic polyester coupled to a peptide produced by a method for coupling amino groups of peptides to carbonyl groups of the polyester, wherein the peptide comprises KGLPLGNSH (SEQ ID NO:3) and wherein the number of amino acid residues in the peptide is up to 50, the method comprising:
 (a) reacting the polyester with oxygen plasma; 
 (b) treating the reacted polyester with alkaline, and 
 (c) coupling the peptide through an N-terminal amino group or an amino group in a side chain of the N-terminal lysine to a carbonyl group of the treated polyester using a cross-linker. 
 
     
     
       9. The biopolymer of  claim 8 , wherein the polyester comprises polylactic acid, poly-L-lactic acid, polyglycolic acid, polyglycolic lactic acid, poly(caprolactone), polyalkyleneoxide-polyalkylene-terephthalate block copolymer, polyethylene terephthalate (PET), polybutylene terephthalate (PBT), or polytrimethylenecaprolactone (PTMC). 
     
     
       10. The biopolymer of  claim 9 , wherein the polyester is poly(caprolactone). 
     
     
       11. The biopolymer of  claim 8 , wherein the peptide is coupled to the carbonyl group of the non-functionalized biopolymer through binding of an amino group in a side chain of the N-terminal lysine of the peptide. 
     
     
       12. The biopolymer of  claim 8 , wherein the cross-linker is a carbodiimide. 
     
     
       13. The biopolymer of  claim 8 , wherein the cross-linker is 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and/or N-hydroxysuccinimide (NHS). 
     
     
       14. The biopolymer of  claim 8 , wherein the biopolymer is comprised within a device.